Biomarkers in Prehospital Rule-out of Intracranial Lesions in TBI Patients (PreTBI I)

Diagnostic Potential of S100B and GFAP in Prehospital Rule-out of Intracranial Lesions in Patients Suffering Mild Traumatic Brain Injury (TBI)

The PreTBI I study will investigate whether prehospital blood samples drawn already in the ambulance can rule-out intracranial lesions in patients suffering head trauma. The study aims to improve triage and treatment of patients suffering mild head trauma, who are considered low-risk patients. These patients do not always benefit from hospitalization, but are nevertheless admitted on precaution, as clinical assesment can be difficult.

Hypotheses:

1. A prehospital measurement of serum S100B ≤ 0,10 microgram/L in mild TBI patients rules out traumatic intracranial lesion with a sensitivity >97%.
2. A prehospital measurement of serum GFAP (glial acidic fibrillary protein) in mild TBI patients rules out traumatic intracranial lesion with sensitivity >97% and results in lower false positive rate than S100B.
3. Prehospital measurements of both GFAP and S100B results in lower false positive rates than in-hospital measurements.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Other: Blood sampling

• Study Type: Observational
• Enrollment (Actual): 595

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Prehospital Emergency Medical Services, Central Denmark Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult patients (≥ 18 years) suffering isolated head trauma and receiving an ambulance dispatched by the prehospital emergency medical services in the Central Denmark Region.

Description

Inclusion Criteria:

• Patients presenting with Glasgow Coma Score (GCS) ≥13-15 and a loss of consciousness for less than 30 min and/or alteration of mental state (being dazed, confused or disorientated) and/or loss of memory for events immediately before and/or after the trauma. The emergency medical service staff will be guided through the inclusion and consent procedures by a simple tablet algorithm.

Exclusion Criteria:

• Patients <18 years, GCS <13, >6 hours elapsed after trauma, unknown time of trauma, multi trauma, known dementia, chronic psychosis or active central nervous system pathology.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Mild TBI patients	Other: Blood sampling; Blood sampling from peripheral venous catheter routinely inserted in trauma patients during transportation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of se-S100B in relation to a binary outcome of clinical patient outcome measured by a yes/no question of "intracranial lesion" pick yes/no	Intracranial lesion comprises abnormal CTC (Marshall Computed Tomography Classification) and/or neurosurgical observation/intervention being death <7 days secondary to head injury or the need of following procedures: craniotomy, elevation of skull fracture, intracranial pressure monitoring or intubation for head injury. Abnormal CTC findings comprise any type of intracranial haemorrhage including subdural, epidural, subarachnoid, intracerebral haemorrhage, edema, pneumocephalus, cerebral contusion or skull cap/base fractures.	in relation to event within 7 days of trauma
Specificity of se-S100B in relation to a binary outcome of clinical patient outcome measured by a yes/no question of "intracranial lesion" pick yes/no	Intracranial lesion comprises abnormal CTC (Marshall Computed Tomography Classification) and/or neurosurgical observation/intervention being death <7 days secondary to head injury or the need of following procedures: craniotomy, elevation of skull fracture, intracranial pressure monitoring or intubation for head injury. Abnormal CTC findings comprise any type of intracranial haemorrhage including subdural, epidural, subarachnoid, intracerebral haemorrhage, edema, pneumocephalus, cerebral contusion or skull cap/base fractures.	in relation to event within 7 days of trauma
Positive predictive value of se-S100B in relation to a binary outcome of clinical patient outcome measured by a yes/no question of "intracranial lesion" pick yes/no	Intracranial lesion comprises abnormal CTC (Marshall Computed Tomography Classification) and/or neurosurgical observation/intervention being death <7 days secondary to head injury or the need of following procedures: craniotomy, elevation of skull fracture, intracranial pressure monitoring or intubation for head injury. Abnormal CTC findings comprise any type of intracranial haemorrhage including subdural, epidural, subarachnoid, intracerebral haemorrhage, edema, pneumocephalus, cerebral contusion or skull cap/base fractures.	in relation to event within 7 days of trauma
Negative predictive value of se-S100B in relation to a binary outcome of clinical patient outcome measured by a yes/no question of "intracranial lesion" pick yes/no	Intracranial lesion comprises abnormal CTC (Marshall Computed Tomography Classification) and/or neurosurgical observation/intervention being death <7 days secondary to head injury or the need of following procedures: craniotomy, elevation of skull fracture, intracranial pressure monitoring or intubation for head injury. Abnormal CTC findings comprise any type of intracranial haemorrhage including subdural, epidural, subarachnoid, intracerebral haemorrhage, edema, pneumocephalus, cerebral contusion or skull cap/base fractures.	in relation to event within 7 days of trauma

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of se-GFAP in relation to a binary outcome of clinical patient outcome measured by a yes/no question of "intracranial lesion" pick yes/no	Intracranial lesion comprises abnormal CTC (Marshall Computed Tomography Classification) and/or neurosurgical observation/intervention being death <7 days secondary to head injury or the need of following procedures: craniotomy, elevation of skull fracture, intracranial pressure monitoring or intubation for head injury. Abnormal CTC findings comprise any type of intracranial haemorrhage including subdural, epidural, subarachnoid, intracerebral haemorrhage, edema, pneumocephalus, cerebral contusion or skull cap/base fractures.	in relation to event within 7 days of trauma
Specificity of se-GFAP in relation to a binary outcome of clinical patient outcome measured by a yes/no question of "intracranial lesion" pick yes/no	Intracranial lesion comprises abnormal CTC (Marshall Computed Tomography Classification) and/or neurosurgical observation/intervention being death <7 days secondary to head injury or the need of following procedures: craniotomy, elevation of skull fracture, intracranial pressure monitoring or intubation for head injury. Abnormal CTC findings comprise any type of intracranial haemorrhage including subdural, epidural, subarachnoid, intracerebral haemorrhage, edema, pneumocephalus, cerebral contusion or skull cap/base fractures.	in relation to event within 7 days of trauma
Positive predictive value of se-GFAP in relation to a binary outcome of clinical patient outcome measured by a yes/no question of "intracranial lesion" pick yes/no	Intracranial lesion comprises abnormal CTC (Marshall Computed Tomography Classification) and/or neurosurgical observation/intervention being death <7 days secondary to head injury or the need of following procedures: craniotomy, elevation of skull fracture, intracranial pressure monitoring or intubation for head injury. Abnormal CTC findings comprise any type of intracranial haemorrhage including subdural, epidural, subarachnoid, intracerebral haemorrhage, edema, pneumocephalus, cerebral contusion or skull cap/base fractures.	in relation to event within 7 days of trauma
Negative predictive value of se-GFAP in relation to a binary outcome of clinical patient outcome measured by a yes/no question of "intracranial lesion" pick yes/no	Intracranial lesion comprises abnormal CTC (Marshall Computed Tomography Classification) and/or neurosurgical observation/intervention being death <7 days secondary to head injury or the need of following procedures: craniotomy, elevation of skull fracture, intracranial pressure monitoring or intubation for head injury. Abnormal CTC findings comprise any type of intracranial haemorrhage including subdural, epidural, subarachnoid, intracerebral haemorrhage, edema, pneumocephalus, cerebral contusion or skull cap/base fractures.	in relation to event within 7 days of trauma

Other Outcome Measures

Outcome Measure	Time Frame
Biomarker dynamics between prehospital and in-hospital se-S100B in relation to a binary outcome of clinical patient outcome measured by a yes/no question of "intracranial lesion" pick yes/no	in relation to event within 7 days of trauma
Biomarker dynamics between prehospital and in-hospital se-GFAP in relation to a binary outcome of clinical patient outcome measured by a yes/no question of "intracranial lesion" pick yes/no	in relation to event within 7 days of trauma
Biomarker dynamics between prehospital and in-hospital combination of se-S100B andse-GFAP values in relation to a binary outcome of clinical patient outcome measured by a yes/no question of "intracranial lesion" pick yes/no	in relation to event within 7 days of trauma

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital; Central Denmark Region

Publications and helpful links

General Publications

• Seidenfaden SC, Kjerulff JL, Juul N, Kirkegaard H, Moller MF, Munster AB, Botker MT. Diagnostic accuracy of prehospital serum S100B and GFAP in patients with mild traumatic brain injury: a prospective observational multicenter cohort study - "the PreTBI I study". Scand J Trauma Resusc Emerg Med. 2021 Jun 2;29(1):75. doi: 10.1186/s13049-021-00891-5.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 15, 2017
• Primary Completion (ACTUAL): February 1, 2019
• Study Completion (ACTUAL): February 1, 2019

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: August 11, 2016
• First Posted (ESTIMATE): August 15, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2019
• Last Update Submitted That Met QC Criteria: April 23, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: Protokol_v2_270616_PreTBI_I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO